Pembrolizumab monotherapy demonstrated promising antitumor activity as a first-line therapy in patients with advanced non-clear cell renal cell carcinoma (nccRCC), particularly those who had papillary or unclassified histology, lead investigator David F. McDermott, MD, of Beth Israel Deaconess Medical Center in Boston, Massachusetts, reported at the 2019 Genitourinary Cancers Symposium.
The finding is from 165 patients enrolled in the KEYNOTE-427 trial, a single-arm, open-label, phase 2 trial examining pembrolizumab. All patients had histologically confirmed nccRCC and had not received prior systemic therapy. Of these patients, 118 had papillary, 21 had chromophobe, and 26 had unclassified histology. The overall objective response rate (ORR) per RECIST v1.1, the primary study end point, was 24.8%. The ORR was 25.4% in patients with papillary tumors, 9.5% for those with chromophobe tumors, and 34.6% for those with unclassified histology.
The ORR was 28.3% and 23.2% for patients who were deemed favorable risk and intermediate/poor risk, respectively, based on International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria, colleagues reported, and the complete response rate was 9.4% and 2.7%, respectively.
The ORR was 33.3% for patients with PD-L1–positive tumors compared with 10.3% for those with PD-L1–negative tumors. In addition, of the 165 patients studied, 91 (55.2%) had a reduction in tumor burden; 20 (12.1%) had an 80% or greater reduction in tumor burden. Seven patients (4.2%) experienced a 100% reduction in tumor burden.
At the time of analysis, 49 patients had died and 3 had withdrawn from the trial. At a median follow-up of 11.1 months (range, 0.9–21.3), 56% of patients discontinued pembrolizumab due to progressive disease or clinical progression.
Grade 3 through grade 5 treatment-related adverse events (TRAEs) occurred in 11% of patients, with 6% discontinuing treatment due to TRAEs. Two patients died from TRAEs (pneumonia and cardiac arrest), according to the investigators.
“We think the results here support further evaluation of pembrolizumab in patients with advanced non-clear cell kidney cancer,” Dr McDermott concluded.
McDermott DF, Lee JL, Ziobro M, et al. First-line pembrolizumab (pembro) monotherapy for advanced non-clear cell renal cell carcinoma (nccRCC): Results from KEYNOTE-427 cohort B. Data presented at: the 2019 Genitourinary Cancers Symposium, San Francisco, CA; February 14-16, 2019. Abstract 546.